G protein-coupled receptors (GPCRs) mediate responses to various extracellular and intracellular cues. However, the large number of GPCR genes and their substantial functional redundancy make it... Show moreG protein-coupled receptors (GPCRs) mediate responses to various extracellular and intracellular cues. However, the large number of GPCR genes and their substantial functional redundancy make it challenging to systematically dissect GPCR functions in vivo. Here, we employ a CRISPR/Cas9-based approach, disrupting 1654 GPCR-encoding genes in 284 strains and mutating 152 neuropeptide-encoding genes in 38 strains in C. elegans. These two mutant libraries enable effective deorphanization of chemoreceptors, and characterization of receptors for neuropeptides in various cellular processes. Mutating a set of closely related GPCRs in a single strain permits the assignment of functions to GPCRs with functional redundancy. Our analyses identify a neuropeptide that interacts with three receptors in hypoxia-evoked locomotory responses, unveil a collection of regulators in pathogen-induced immune responses, and define receptors for the volatile food-related odorants. These results establish our GPCR and neuropeptide mutant libraries as valuable resources for the C. elegans community to expedite studies of GPCR signaling in multiple contexts. Show less
Food security and sustainable development of agriculture has been a key challenge for decades. To support this, nanotechnology in the agricultural sectors increases productivity and food security,... Show moreFood security and sustainable development of agriculture has been a key challenge for decades. To support this, nanotechnology in the agricultural sectors increases productivity and food security, while leaving complex environmental negative impacts including pollution of the human food chains by nanoparticles. Here we model the effects of silver nanoparticles (Ag-NPs) in a food chain consisting of soil-grown lettuce Lactuca sativa and snail Achatina fulica. Soil-grown lettuce were exposed to sulfurized Ag-NPs via root or metallic Ag-NPs via leaves before fed to snails. We discover an important biomagnification of silver in snails sourced from plant root uptake, with trophic transfer factors of 2.0–5.9 in soft tissues. NPs shifts from original size (55–68 nm) toward much smaller size (17–26 nm) in snails. Trophic transfer of Ag-NPs reprograms the global metabolic profile by down-regulating or up-regulating metabolites for up to 0.25- or 4.20- fold, respectively, relative to the control. These metabolites control osmoregulation, phospholipid, energy, and amino acid metabolism in snails, reflecting molecular pathways of biomagnification and pontential adverse biological effects on lower trophic levels. Consumption of these Ag-NP contaminated snails causes non-carcinogenic effects on human health. Global public health risks decrease by 72% under foliar Ag-NP application in agriculture or through a reduction in the consumption of snails sourced from root application. The latter strategy is at the expense of domestic economic losses in food security of $177.3 and $58.3 million annually for countries such as Nigeria and Cameroon. Foliar Ag-NP application in nano-agriculture has lower hazard quotient risks on public health than root application to ensure global food safety, as brought forward by the United Nations Sustainable Development Goals. Show less
Metal uptake and distribution in crops have been demonstrated to be highly variable and depending on the metal of interest and the crop type. However, no consensus is reached regarding the primary... Show moreMetal uptake and distribution in crops have been demonstrated to be highly variable and depending on the metal of interest and the crop type. However, no consensus is reached regarding the primary factor controlling metal uptake in crops. This study thus comparably investigated Hg, As, Zn, Pb, Cd and Cu uptake and distribution in three crops grown in a watershed near a copper mining field located in Yunnan, Southwestern China. The bioconcentration factor (BCF) and translocation factor (TF) were statistically compared for the same metal across different crops. Leafy crops had a stronger propensity to accumulate Hg, As and Zn than fruit crops. The ability of grain crops to accumulate Cd and Cu was much lower than leafy and fruit crops. The three crops all tended not to accumulate Pb in their edible tissues. The DTPA extracted metal concentrations were not statistically correlated with the metal concentrations in crop edible tissues. It is thus not practical to predict metal uptake of Hg, As, Pb and Zn through their available concentrations in soils. The contents of nitrogen and phosphorus, and competing metal ions present in paddy soil decreased the accumulation of Cu and Cd in rice grains. By means of hierarchical cluster analysis, the high accumulation of Zn in the edible tissues of fruit and grain crops was mainly due to dust inputs via phloem transport from leaves. This is why BCF(Zn) was the highest among the six metals for these two crops. For leafy crops, the accumulation of Hg, Cd and Zn in leaves was mainly through soil inputs by roots. Our findings serve as a scientific basis for the selection of crops in areas with high background of heavy metals. Show less
Societal Impact Statement Combining natural and social science approaches to conduct archeological research on wooden cultural relics is important for exploring major aspects of ancient... Show moreSocietal Impact Statement Combining natural and social science approaches to conduct archeological research on wooden cultural relics is important for exploring major aspects of ancient civilizations. The Forbidden City in Beijing, China, is the largest existing wooden palace complex in the world. We examined ancient DNA of imperial wood "Nanmu" specimens taken from representative structural components of the Forbidden City, in order to provide a new perspective on the long-standing dispute about its species. This allowed us to accurately identify and properly restore these wooden artifacts and improved our understanding of the past interactions between plant distribution, forest resources, and human activities. Exploring the life styles and production methods of past generations using plant resources can help us to improve our understanding of human civilization. Nanmu, known for its high wood quality, was exclusively used for imperial palace construction in the 15th-19th centuries in China, yet its species has been a subject of long-standing debate. Here, we revisit this unresolved problem, using morphology and ancient DNA (aDNA) to analyze 21 centuries-old Nanmu specimens sampled from representative palaces of the Forbidden City. Cytochemical staining demonstrated that endogenous aDNA sporadically occurs in the wood ray parenchyma cells of Nanmu specimens. High-quality plastid genomes were retrieved from archeological woods for the first time via an aDNA capture method, with 90%-100% coverage (137,663-152,805 bp) and sequence depths of 27.05- to 1409.94-fold. Utilizing these ancient genomes, our results demonstrate that Phoebe zhennan and Phoebe hui are most likely the main species of Nanmu in the Forbidden City. This finding diverges from the prevailing view that Nanmu encompasses woods from the whole genus Phoebe and even its close relative Machilus. It also shows that stringent criteria were used when selecting construction materials for the Forbidden City. By combining morphological traits with aDNA analyses, we provide a new solution for identifying the species of timber used for ancient architecture, and we increase our understanding of the way in which forest resources were recognized and utilized by our ancestors despite the lack of a plant taxonomic framework in ancient times. Show less
Human society operates on large-scale cooperation. However, individual differences in cooperativeness and incentives to free ride on others' cooperation make large-scale cooperation fragile and can... Show moreHuman society operates on large-scale cooperation. However, individual differences in cooperativeness and incentives to free ride on others' cooperation make large-scale cooperation fragile and can lead to reduced social welfare. Thus, how individual cooperation spreads through human social networks remains puzzling from ecological, evolutionary, and societal perspectives. Here, we identify oxytocin and costly punishment as biobehavioral mechanisms that facilitate the propagation of cooperation in social networks. In three laboratory experiments (n = 870 human participants: 373 males, 497 females), individuals were embedded in heterogeneous networks and made repeated decisions with feedback in games of trust (n = 342), ultimatum bargaining (n = 324), and prisoner's dilemma with punishment (n = 204). In each heterogeneous network, individuals at central positions (hub nodes) were given intranasal oxytocin (or placebo). Giving oxytocin (vs matching placebo) to central individuals increased their trust and enforcement of cooperation norms. Oxytocin-enhanced norm enforcement, but not elevated trust, explained the spreading of cooperation throughout the social network. Moreover, grounded in evolutionary game theory, we simulated computer agents that interacted in heterogeneous networks with central nodes varying in terms of cooperation and punishment levels. Simulation results confirmed that central cooperators' willingness to punish noncooperation allowed the permeation of the network and enabled the evolution of network cooperation. These results identify an oxytocin-initiated proximate mechanism explaining how individual cooperation facilitates network-wide cooperation in human society and shed light on the widespread phenomenon of heterogeneous composition and enforcement systems at all levels of life. Show less
This paper examines mentorship as a mechanism for individuals to acquire and develop creativity. More specifically, we study the effect of mentor creativity on protégé creativity and how this... Show moreThis paper examines mentorship as a mechanism for individuals to acquire and develop creativity. More specifically, we study the effect of mentor creativity on protégé creativity and how this effect is moderated by the mentoring styles of autonomy and exploration. Our empirical analysis focuses on formal PhD supervision and training, drawing on survey and bibliometric data for 143 life-science professors (mentors) and their 685 PhD students (protégés). We find that the effect of mentor creativity on protégé creativity is insignificant during protégés’ PhD studies but becomes significantly positive after protégés hold faculty positions, suggesting that the mentorship effect takes time to manifest but is enduring. Furthermore, the effect of mentor creativity on protégé creativity is significant only when protégés have high levels of autonomy and exploration during PhD studies. This suggests the importance of autonomy and exploration in the effective transfer of creativity from mentors to protégés. Show less
The northern white rhinoceros (NWR) is probably the earth's most endangered mammal. To rescue the functionally extinct species, we aim to employ induced pluripotent stem cells (iPSCs) to generate... Show moreThe northern white rhinoceros (NWR) is probably the earth's most endangered mammal. To rescue the functionally extinct species, we aim to employ induced pluripotent stem cells (iPSCs) to generate gametes and subsequently embryos in vitro. To elucidate the regulation of pluripotency and differentiation of NWR PSCs, we generated iPSCs from a deceased NWR female using episomal reprogramming, and observed surprising similarities to human PSCs. NWR iPSCs exhibit a broad differentiation potency into the three germ layers and trophoblast, and acquire a naïve-like state of pluripotency, which is pivotal to differentiate PSCs into primordial germ cells (PGCs). Naïve culturing conditions induced a similar expression profile of pluripotency related genes in NWR iPSCs and human ESCs. Furthermore, naïve-like NWR iPSCs displayed increased expression of naïve and PGC marker genes, and a higher integration propensity into developing mouse embryos. As the conversion process was aided by ectopic BCL2 expression, and we observed integration of reprogramming factors, the NWR iPSCs presented here are unsuitable for gamete production. However, the gained insights into the developmental potential of both primed and naïve-like NWR iPSCs are fundamental for in future PGC-specification in order to rescue the species from extinction using cryopreserved somatic cells. Show less
Study Design: Questionnaire-based survey.Objectives: Surgical site infection (SSI) is a common complication in spine surgery but universal guidelines for SSI prevention are lacking. The objectives... Show moreStudy Design: Questionnaire-based survey.Objectives: Surgical site infection (SSI) is a common complication in spine surgery but universal guidelines for SSI prevention are lacking. The objectives of this study are to depict a global status quo on implemented prevention strategies in spine surgery, common themes of practice and determine key areas for future research.Methods: An 80-item survey was distributed among spine surgeons worldwide via email. The questionnaire was designed and approved by an International Consensus Group on spine SSI. Consensus was defined as more than 60% of participants agreeing to a specific prevention strategy.Results: Four hundred seventy-two surgeons participated in the survey. Screening for Staphylococcus aureus (SA) is not common, whereas preoperative decolonization is performed in almost half of all hospitals. Body mass index (BMI) was not important for surgery planning. In contrast, elevated HbAIc level and hypoalbuminemia were often considered as reasons to postpone surgery. Cefazoline is the common drug for antimicrobial prophylaxis. Alcohol-based chlorhexidine is mainly used for skin disinfection. Double-gloving, wound irrigation, and tissue-conserving surgical techniques are routine in the operating room (OR). Local antibiotic administration is not common. Wound closure techniques and postoperative wound dressing routines vary greatly between the participating institutions.Conclusions: With this study we provide an international overview on the heterogeneity of SSI prevention strategies in spine surgery. We demonstrated a large heterogeneity for pre-, peri- and postoperative measures to prevent SSI. Our data illustrated the need for developing universal guidelines and for testing areas of controversy in prospective clinical trails. Show less
Despite the value of technology integration for educational equity and quality being emphasized by numerous studies, many gaps exist about how technology integration can be approached in policy... Show moreDespite the value of technology integration for educational equity and quality being emphasized by numerous studies, many gaps exist about how technology integration can be approached in policy plans, implemented in pedagogical practices, and embraced by teachers, students, and parents. In the current dissertation, the focus is on teachers’ pedagogical practices with technology in primary and secondary education, contributing to a more detailed understanding of what happens to integrate technology into the teaching and learning processes. Given this goal, we examined the different teaching and technology practices considering the concerted efforts of various stakeholders at different levels and contexts. Five studies were performed on: (1) an overview of the link between local information and communications technology (ICT) policy plans and the ICT practices of rural schools; (2) rural teachers’ use of digital educational resources aimed at promoting digital equity and education for all; (3) rural teachers’ sharing of digital educational resources aimed at promoting teacher professional learning opportunities and development; (4) (a meta-analysis on) the effectiveness of various mobile technology usage on learning outcomes in primary and secondary education; (5) the relationships among teacher beliefs, classroom process quality, and student engagement in smart classroom learning environments in secondary education. Show less
Chapter 3 examines the decisions that inform the BRI’s institution building.It explores the tension between strategic and effficiency-oriented concerns, tracing these tensions across three issue... Show moreChapter 3 examines the decisions that inform the BRI’s institution building.It explores the tension between strategic and effficiency-oriented concerns, tracing these tensions across three issue areas: tax, trade, and development finance. The chapter shows that, in dealing with challenges, the Chinese government lacks an integral governance framework that systemically coordinates all relevant institutions. Instead, it takes varied institutional approaches to overseeing BRI projects, ranging from bilateral trade agreements to multilateral fijinancial institutions. This raises the question of what is driving China’s development of agreements and institutions for the BRI. The chapter argues that China’s development of BRI tax initiatives is mostly motivated by efficiency drivers, its trade agreements with key BRI partners by strategic drivers, and its efforts to establish multilateral financial institutions by both drivers. Show less